Escargot (esg) is a gene in the Snail family of genes in fruit flies. After a certain point, it doesn't really help all that much to peer too closely at the nomenclature of genes - it is best to just accept it and move on. Reduced levels of esg modestly extend life in flies, as researchers here demonstrate. As to why this is the case, here as in so many other cases, understanding is lacking. There are a few core mechanisms of plasticity in aging, linking the operation of cellular metabolism to natural variations in longevity between individuals. These largely relate to the activation of stress responses due to environmental circumstances, such as a lack of nutrients, but an enormous number of genes and proteins can influence those core mechanisms. The map of cellular biochemistry is far from complete in all of its details, and thus sometimes all that can be done is to look at relationships and speculate.
The nervous system is a key player in maintaining homeostasis and the structural and functional integrity of living beings and, hence, in controlling aging and longevity. Given the role of the nervous system in life span control, a reasonable question would be whether genes defining the cellular specificity of neurons are also involved, in some way, in the regulation of longevity.
We have already demonstrated that several genes that encode RNA polymerase II transcription factors and that are involved in neural development affect life span in Drosophila melanogaster. Among other genes, escargot (esg) was identified as a candidate gene affecting life span in a screen of more than 1,500 insertion mutations and the insertion located downstream of esg was further confirmed to be causally associated with life span control.
The gene esg belongs to the Snail family of genes that are involved in the development of the nervous system in arthropods and chordates. In Drosophila melanogaster, Esg and other Snail proteins act to control asymmetric neuroblast division during embryogenesis; however, Esg functions are not exclusively neuronal, and it also participates in the maintenance of intestinal and male germ cells, regulates tracheal morphogenesis and development of the genital disk, and determines wing cell fate.
Here, we present new data on the role of esg in life span control. Analysis of the esg-BG01042 mutation allowed us to show that esg is involved in the regulation of life span, to varying degrees, in unmated and mated males and females. The esg-BG01042 mutation also increased locomotion, specifically during old age, indicating that the mutation slowed down aging. The increase in longevity was caused by decreased esg transcription associated with structural changes in the DNA sequences downstream of the gene.
Targets of esg encoded enzymes involved in the biosynthesis of neurotransmitters, neuropeptides, cationic transporters, and other proteins. Among others, genes involved in the defense/immune response were both up- and down-regulated. Of the genes known to be involved in life span control, at least two genes associated with increased life span, heat shock protein 26 (hsp26) and NAD-dependent methylenetetrahydrofolate dehydrogenase (Nmdmc), increased transcription.